| Structural highlights
2wip is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | ,
| | Related: | 1h08, 1pye, 2vth, 2b53, 1v1k, 1okv, 1h25, 1ke7, 1pxk, 2wih, 2bhh, 2vta, 2uue, 1gz8, 1e1v, 1ol2, 1h27, 1jsv, 2wha, 2b52, 1ke5, 1fin, 2c5o, 2c68, 2vtt, 1p2a, 2vtq, 2c4g, 1w0x, 1h1q, 2w05, 1pxo, 1ke9, 1hck, 2a0c, 1jsu, 1pxn, 2uze, 2vtm, 2v0d, 1oiq, 1h1r, 2iw8, 1hcl, 1pw2, 1gih, 2whb, 2vtn, 2w06, 1jst, 1oiu, 1b38, 1pxm, 1fq1, 1vyw, 1h1p, 2c69, 1urc, 1pxi, 2c6i, 1ykr, 2w17, 2c5y, 2uzd, 2c6k, 1wcc, 2j9m, 1vyz, 2vti, 1jvp, 1w98, 1pkd, 1p5e, 2vts, 2c5p, 2uzn, 2b54, 1ke6, 1pxj, 2uzl, 2cci, 2bkz, 2g9x, 1y91, 2iw6, 1gij, 1r78, 1h0v, 2iw9, 1w8c, 1buh, 2bpm, 2bts, 1fvv, 1okw, 2vtp, 2a4l, 2c6t, 1fvt, 1qmz, 2w1h, 2vu3, 1ogu, 2b55, 1pf8, 1h1s, 2c5v, 2jgz, 2bhe, 1urw, 1oiy, 2c6l, 1f5q, 2c6o, 2vtl, 1ol1, 2uzb, 2wfy, 1h01, 1oir, 1oi9, 2vtj, 2cjm, 2wev, 2c5x, 2c5n, 2c6m, 1oit, 1gy3, 2v22, 1di8, 1gii, 2vv9, 1e9h, 2vto, 1dm2, 2uzo, 1h24, 2exm, 1h00, 2clx, 1pxp, 2cch, 1b39, 2btr, 1aq1, 1h0w, 1g5s, 1ckp, 1pxl, 1h28, 1ke8, 2vtr, 1h26, 1e1x, 1h07, 1y8y |
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The discovery of a novel class of inhibitors of cyclin dependent kinases (CDKs) is described. Starting from compound 1, showing good potency as inhibitor of CDKs but being poorly selective against a panel of serine-threonine and tyrosine kinases, new analogues were synthesized. Enhancement in selectivity, antiproliferative activity against A2780 human ovarian carcinoma cells, and optimization of the physical properties and pharmacokinetic profile led to the identification of highly potent and orally available compounds. Compound 28 (PHA-848125), which in the preclinical xenograft A2780 human ovarian carcinoma model showed good efficacy and was well tolerated upon repeated daily treatments, was identified as a drug candidate for further development. Compound 28 is currently undergoing phase I and phase II clinical trials.
Identification of N,1,4,4-Tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydr o-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a Potent, Orally Available Cyclin Dependent Kinase Inhibitor.,Brasca MG, Amboldi N, Ballinari D, Cameron A, Casale E, Cervi G, Colombo M, Colotta F, Croci V, D'Alessio R, Fiorentini F, Isacchi A, Mercurio C, Moretti W, Panzeri A, Pastori W, Pevarello P, Quartieri F, Roletto F, Traquandi G, Vianello P, Vulpetti A, Ciomei M J Med Chem. 2009 Jul 15. PMID:19603809[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Brasca MG, Amboldi N, Ballinari D, Cameron A, Casale E, Cervi G, Colombo M, Colotta F, Croci V, D'Alessio R, Fiorentini F, Isacchi A, Mercurio C, Moretti W, Panzeri A, Pastori W, Pevarello P, Quartieri F, Roletto F, Traquandi G, Vianello P, Vulpetti A, Ciomei M. Identification of N,1,4,4-Tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydr o-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a Potent, Orally Available Cyclin Dependent Kinase Inhibitor. J Med Chem. 2009 Jul 15. PMID:19603809 doi:10.1021/jm9006559
|
